Utility of measuring serum or red blood cell folate in the era of folate fortification of flour

Clin Biochem. 2014 May;47(7-8):533-8. doi: 10.1016/j.clinbiochem.2014.01.023. Epub 2014 Jan 31.


Folic acid is an essential nutrient involved in one-carbon metabolism. Insufficient folate can result in megaloblastic anemia and an increased risk of neural tube defects. In response to the latter, some governments have mandated the fortification of flour with folate. This had resulted in a documented rise in the serum and red blood cell folate levels in the population. This has impacted the potential utility of folate measurements to detect folate deficiency in the clinical context. Folate measurements, whether done in serum or red blood cells, are subject to analytical variation, especially the latter, which also affects the utility of such measurements. Examining the literature reveals that in clinical situations, generally <1% of the subjects will have folate deficiency regardless of potentially pre-disposing factors (e.g. anemia, anti-folate agents, inflammatory bowel disease). Data from our center for both pediatric and adult populations is presented that supports this observation. Consequently, there exists very few indications for folate determinations (unexplained macrocytosis, inborn errors of metabolism) and it may be more efficient to simply treat suspected cases.

Keywords: Folate; Folic acid; Fortification; Red blood cells; Serum; Test utility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Erythrocytes / metabolism
  • Flour*
  • Folic Acid / administration & dosage*
  • Folic Acid / blood*
  • Folic Acid Deficiency / blood
  • Folic Acid Deficiency / diagnosis
  • Humans


  • Folic Acid